1. Technical Field
The present invention generally relates to a method and algorithm for spatially identifying sources generative of cardiac fibrillation, and in particular, atrial fibrillation.
2. Related Art
2a. Atrial Fibrillation: Epidemiology, Incidence and Prevalence
Atrial fibrillation (AF) is the most frequently occurring sustained cardiac rhythm disturbance (“arrhythmia”) in humans. AF may be intermittent or paroxysmal, or it may be a stable arrhythmia that may last for many years. One to two million Americans have chronic AF. Epidemiologic studies have shown that the prevalence and incidence of AF doubles with each advancing decade beyond 50 years of age. Although not usually considered a life-threatening arrhythmia, AF has been associated with a two-fold increase in total and cardiovascular mortality. Factors that may increase mortality in AF include age, mitral stenosis, aortic valve disease, coronary artery disease, hypertension, and congestive heart failure.
Clinically, AF is often categorized as:
[i] paroxysmal—generally characterized by predominant sinus rhythm with intermittent episodes of AF;
    [ii] chronic—persistent or permanent AF;    [iii] acute—an episode of AF with an onset within 24 to 48 hours of diagnosis; and,    [iv] lone—variably defined, but generally considered to occur in the absence of cardiac disease.
The most clinically important consequences of AF are thromboembolic events and stroke. A four-fold to six-fold increased risk of stroke (15-fold in patients with a history of rheumatic heart disease) makes this arrhythmia one of the most potent risk factors for stroke in the elderly and the most common cause of cardiogenic stroke. The risk of stroke in nonvalvular AF varies with age and with the presence of concomitant cardiovascular disease and other risk factors for stroke. Most strokes associated with AF appear to be caused by cardiac emboli, presumably formed in fibrillating atria.
The presence of persistent rapid ventricular rates in association with AF may lead to impairment of ventricular function by a mechanism similar to that of tachycardia-mediated cardiomyopathy. This condition may be reversible. Improved ventricular function has been reported after complete atrioventricular (AV) node ablation, medical control of ventricular rate, or achievement of sinus rhythm. Evidence for development of atrial myopathy has also been reported in patients with AF in the absence of valvular disease. Mechanical and electrical cardiac remodeling could also promote further propensities toward AF and thromboembolism.
The most common underlying cardiovascular diseases associated with AF are hypertension and ischemic heart disease. Valvular heart disease, congestive heart failure, hypertension, and diabetes have been shown to be independent risk factors for AF. Other associated conditions include pulmonary embolism, thyrotoxicosis, chronic obstructive pulmonary disease, the Wolff-Parkinson-White syndrome, pericarditis, neoplastic disease, and the postoperative state. The cardiac rhythm of a normal heart may be precipitated into AF by excessive alcohol, stress, drugs, excessive caffeine, hypoxia, hypokalemia, hypoglycemia, and systemic infection.
Morbidity attributable to AF also includes limitation in functional capacity from symptoms of palpitations, fatigue, dyspnea, angina, or congestive heart failure.
2b. Normal Cardiac Electrophysiology
The heart is a blood pumping organ consisting of four chambers—two atria and two ventricles. The normal function of the heart depends on the periodic and synchronized contraction of the walls of its four chambers. The walls of the heart are comprised of millions of cells called cardiomyocytes, whose interiors are maintained at a transmembrane potential difference voltage of about 70 millivolts relative to the external environment; i.e., the cardiomyocytes are in a state of relative voltage polarization. The synchronized mechanical contraction of the walls of the heart's chambers is triggered by the sequential and coordinated depolarization of their cardiomyocytes. The measured aggregate manifestation this depolarization of the resting transmembrane potential difference in cardiomyocytes is called an action potential or depolarization impulse.
The normal propagation of every cardiac action potential starts spontaneously at a region of the heart's right atrium (“RA”) known as the sino-atrial (“SA”) node, from which the action potential spreads throughout both atrial walls, causing their synchronous contraction, and toward a region known as the atrio-ventricular (“AV”) node. From AV node, the action potential propagates as a depolarization wave front into a specialized conduction system known as the His-Purkinje system, whose terminal branches conduct the action potential into the walls of the right and left ventricles.
The normal propagation of the action potential's wave front of depolarization in the walls the atria and the ventricles is relatively continuous and uninterrupted. The normal contraction of the heart accompanying the propagation of the depolarization wave front is called normal sinus rhythm (“NSR”). NSR depends on normal propagation of the action potential, which must always originate at the SA node, as opposed to some other ectopic focus of origin, and must always spread from the SA node precisely in the foregoing sequence of transmission to the AV node, and thence to and through the His-Purkinje conduction system.
2c. Electrophysiology of Atrial Fibrillation
Certain self-sustaining, irregular and non-physiologically sequential depolarization impulses (“arrhythmias”) may arise from one or more ectopic (non-SA node—either pacemaker or reentrant) foci and either impair or eliminate the normal contracting rhythm of the heart, thereby impairing or destroying the heart's capacity to pump blood. Atrial fibrillation and ventricular fibrillation are two such arrhythmias.
During atrial fibrillation (“AF”), multiple depolarization wave fronts are generated in the atria, giving rise to vermiform atrial contractions responding to depolarization wave fronts that often have frequencies in excess of 400 cycles per minute. This rapid, disordered atrial activation results in loss of coordinated atrial contraction, with irregular electrical conduction to the AV node and His-Purkinje system, leading to sporadic ventricular contractions.
On the surface electrocardiogram (“ECG”), AF is characterized by the absence of visible discrete P waves or the presence of irregular fibrillatory waves, or both, and an irregular ventricular response.
Sustained AF depends on the uninterrupted aberrant periodic electrical activity of at least one discrete primary ectopic focus, hereinafter called a sustaining source of fibrillatory activity (“SSFA”) that may behave as a reentrant circuit. The reentrant circuit is established by the interaction of propagating wave fronts of cardiac depolarization with either an anatomical or functional obstacles, i.e., tissue regions of variable refractoriness or excitability acting as intermittent conduction blocks, in a region of the heart, such as, for example the right atrium (“RA”) or the right ventricle (“RV”) in a process called “vortex shedding.” These reentrant circuits act as sources (“mother rotors”) that generate high-frequency depolarization wave fronts (“mother waves”) emanating in rapid succession that propagate through both atria and interact with anatomic or functional obstacles acting as intermittent conduction blocks and maintaining the overall fibrillatory activity. Some of these anatomic or functional obstacles become secondary ectopic foci themselves generative of aberrant depolarization daughter wavelets having lower frequencies.
Some of these daughter wavelets may attenuate in amplitude and undergo decremental conduction. Others may be annihilated by collision with another daughter wavelet or a boundary; and, still others conduct circuitously to create new vortices of depolarization. The end result is the fragmentation or fractionation of the secondary depolarizing wave fronts emanating from these reentrant circuits into multiple independent daughter wavelets, giving rise to new wavelets, and so on—in a perpetual, globally aperiodic pattern that characterizes fibrillatory conduction.
Sustained AF is a function of several factors, including a nonuniform distribution reentrant circuits having relatively brief refractory periods over a sufficiently large area of cardiac tissue with the concomitant fractionation of a mother wave into a large number of independent daughter wavelets, possibly also having low conduction velocities.
2d. Atrial Fibrillation: Therapeutic Approaches
Radiofrequency (“RF”) ablation of atrial tissue by application of energy through cardiac catheters has become a major therapeutic method for atrial fibrillation in patients. The RF ablation procedure consists of beneficially altering the electrical properties of cardiac tissue in the vicinity of the ablating catheter tip. The extent to which tissue is altered depends on the power and duration of the application, as well as on the characteristics of the tissue itself. For a typical RF ablation, a power of 20–40 Watts is delivered for 6–10 minutes to create an altered substrate in a cardiac volume with a radius of about 5 mm around the catheter tip.
The efficacy of RF ablation is suboptimal because of imprecise localization of tissue hosting the AF sources that are targeted. This situation prevails because methods for mapping sources of fibrillation rely on educated guesswork based upon subjective inferences from clinical electrophysiological data and vague identification criteria. Extensive ablation sufficient to modify cardiac tissues can cure many types of AF, but it exposes the patient to a higher risk of complications and to unacceptable fluoroscopy exposure times; on the other hand, more selective ablation that targets localized ectopic foci is safer, but may be less likely to effect a permanent cure of the AF, which may be become prone to recurrences. Accordingly, there is a need for improved targeting of RF ablation and other surgical interventions that seek to neutralize AF.
The present invention comprises an automated method for the detection and spatial identification of sources of fibrillation that is far more rapid and reliable than prevailing methods. Accordingly, the present invention may be expected to substantially reduce the duration of RF ablation and improve the success rate of the procedure by providing real-time spectrally guided RF ablation in patients.